Managing a Patient Presenting With Chest Pain and Gastrointestinal Complaints Using Dupilumab.

Adverse drug reactions or adverse drug events account for a significant proportion of emergency department visits among children and adolescents. Unfortunately, rare reactions to medications may go unnoticed by clinicians due to a lack of reporting to drug surveillance and monitoring programs. We present the case of an 18-year-old male who visited the emergency department on two separate occasions after receiving dupilumab injections for his atopic dermatitis. Ten days prior to his presentation, he was evaluated in the emergency room for the onset of chest pain, five days following his first dupilumab injection. Investigations in the interim revealed no cardiac pathology. He presented with a complaint of severe abdominal pain associated with nausea and vomiting several hours after receiving his second dupilumab injection. Investigations for causes of acute gastrointestinal or anaphylactic reactions only revealed mild leukocytosis and hypokalemia. A definitive diagnosis of hypersensitivity reaction, such as anaphylaxis or serum-sickness-like reaction, could not be made at either emergency visit due to the lack of objective findings and few similar reported cases. However, the timing of each event made an adverse reaction highly suspicious as the inciting factor of this patient's symptoms. He received oral potassium, ketorolac, and ondansetron for headache and ongoing nausea respectively. He was discharged home within a few hours after his symptoms had resolved. The limited reports and evidence of these symptoms being associated with dupilumab injections made it difficult to reach a definitive diagnosis. However, a holistic review of the patient's history, medication list, and contextual factors revealed that a rare adverse drug reaction was a possible inciting factor on each separate occasion. Further research is required to determine the frequency and explore the existence of any causal relationship between dupilumab treatment and chest pain or gastritis in adolescent populations.

Comparison of Local Recurrence After Simple and Skin-Sparing Mastectomy Performed in Patients with Ductal Carcinoma In Situ.

BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) is increasing with the use of screening mammography, and approximately 30% of all women diagnosed with DCIS are treated by mastectomy. There is increasing use of a skin-sparing mastectomy (SSM) approach to surgically excise DCIS as this facilitates immediate breast reconstruction. The rates of locoregional recurrence (LRR) after simple mastectomy performed for pure DCIS are historically reported as 1%; however, international data suggest that LRR after SSM may be higher. METHODS: To determine our rates of LRR and compare the effect of the type of mastectomy performed, we undertook a retrospective review of all patients who underwent a mastectomy for pure DCIS at our institution between 2000 and 2010. RESULTS: In total, 199 patients underwent a mastectomy for pure DCIS (with eight local recurrences), all of which were invasive ductal carcinoma. The recurrences all occurred after SSM, which was associated with a higher 5-year LRR of 5.9% (5/102) compared with 0% in the simple mastectomy group (0/97; p = 0.012), log-rank. Univariate analysis showed the two factors that predicted the risk of recurrence were a young age at mastectomy and close or involved margins. CONCLUSIONS: These data highlight the importance of achieving clear margins, especially in young women with estrogen receptor-negative DCIS who have a higher risk of invasive recurrence. Women undergoing a mastectomy for DCIS should be counseled as to the importance of achieving clear margins and the potential increased need for further excision, post-mastectomy radiotherapy and post-reconstruction mammography in order to prevent LRR after SSM.

Anatomic Relationships of the Distal and Proximal Radioulnar Joints Articulating Surface Areas and of the Radius and Ulna Bone Volumes - Implications for Biomechanical Studies of the Distal and Proximal Radioulnar Joints and Forearm Bones.

BACKGROUND: Previous work from this laboratory has evidenced the biomechanical role of forearm osseoligamentous structures in load transfer of applied forces. It has shown that forces transmitted across the distal radioulnar joint (DRUJ) and proximal radioulnar joint (PRUJ) are similar, though not identical, under axial loading conditions. The purpose of the study was to assess the articulating surface areas of the radioulnar joints and the volumes of the forearm bones addressing the hypothesis that there may be anatomic adaptations that reflect the biomechanical function of the integrated forearm unit. METHODS: The articulating surface areas of PRUJ and DRUJ were assessed using a laser scanner in 24 cadaver forearms. The articulating joint surfaces were additionally delineated from standardized photographs assessed by three observers. The surface areas of matched pairs of joints were compared on the null hypothesis that these were the same within a given forearm specimen. An additional 44 pairs of matched forearm bone volumes were measured using water displacement technique and again compared through statistical analysis (paired sample t-test and Bland-Altman analysis). RESULTS: The findings of this study are that the articulating surface areas of the DRUJ and PRUJ as well as the bone volumes are significantly different and, yet, strongly correlated. The paired sample t-test showed a significant difference between the surface areas of the DRUJ and PRUJ (p < 0.05). The PRUJ articulating surface area was marginally larger than the DRUJ with a PRUJ:DRUJ ratio of 1.02. Paired sample t-test showed a significant difference between the two bone volumes (p < 0.01) with a radius to ulna bone volume ratio of 0.81. When the olecranon was disregarded, radius volume was on average of 4% greater than ulna volume. CONCLUSION: This study demonstrates and defines the anatomical relationships between the two forearm bones and their articulating joints when matched for specimen. The data obtained are consistent with the theory of integrated forearm function generated from published biomechanical studies.

Acute high-fat feeding does not prevent the improvement in glucose tolerance after resistance exercise in lean individuals.

Our first aim was to investigate whether the ingestion of a single high-fat meal impairs glucose tolerance. Our second aim was to investigate whether improvements in glucose tolerance that are seen after resistance exercise remain when exercise is performed after ingestion of a high-fat meal. Eight young males consumed either a high fat (HF) or an isocaloric control (CON) meal in the morning and underwent an oral glucose tolerance test (OGTT) 6 h later. On two other occasions, a single 1 h bout of resistance exercise was completed 2 h after consumption of each meal (HFE and CONE). There were no significant differences in plasma glucose and plasma insulin areas under the curve (AUC) or estimates of insulin sensitivity between the HF and CON trials (P > 0.05). The HFE and CONE trials elicited a ~20% lower plasma glucose AUC (P < 0.05) compared to their respective control trials. The HFE also elicited a ~25% lower plasma insulin AUC (P < 0.05) in comparison to the HF trial. The HFE trial also significantly improved estimates of insulin sensitivity in comparison to the HF condition (P < 0.05). In conclusion, this study demonstrates that consumption of a single HF meal does not impair glucose tolerance in the resting state in lean individuals and that an acute bout of resistance exercise remains effective in enhancing glucose tolerance following the ingestion of a single high-fat meal.

Qualitatively modelling and analysing genetic regulatory networks: a Petri net approach.

MOTIVATION: New developments in post-genomic technology now provide researchers with the data necessary to study regulatory processes in a holistic fashion at multiple levels of biological organization. One of the major challenges for the biologist is to integrate and interpret these vast data resources to gain a greater understanding of the structure and function of the molecular processes that mediate adaptive and cell cycle driven changes in gene expression. In order to achieve this biologists require new tools and techniques to allow pathway related data to be modelled and analysed as network structures, providing valuable insights which can then be validated and investigated in the laboratory. RESULTS: We propose a new technique for constructing and analysing qualitative models of genetic regulatory networks based on the Petri net formalism. We take as our starting point the Boolean network approach of treating genes as binary switches and develop a new Petri net model which uses logic minimization to automate the construction of compact qualitative models. Our approach addresses the shortcomings of Boolean networks by providing access to the wide range of existing Petri net analysis techniques and by using non-determinism to cope with incomplete and inconsistent data. The ideas we present are illustrated by a case study in which the genetic regulatory network controlling sporulation in the bacterium Bacillus subtilis is modelled and analysed. AVAILABILITY: The Petri net model construction tool and the data files for the B. subtilis sporulation case study are available at http://bioinf.ncl.ac.uk/gnapn.